Monday, March 01, 2021

AGBT21: Rebus Esper for Spatial Sees Things You Wouldn't Believe

My prediction that spatial would be a hot topic at AGBT was easy to make knowing I was sitting on embargoed news in the spatial space.  This morning Rebus Biosystems announced the launch of the Rebus Esper system for wide field spatial profiling of gene panels with subcellular resolution.  Rebus is promising that this instrument will offer true walkaway automation from fluidics through imaging, and data processing, requiring only one hour of hands-on time.
Esper will be a floor-standing instrument; the company is holding the cost close to the vest but says it will be on par with other mid-range equipment -- so perhaps in the quarter to three quarter million dollar range.  Consumable costs are also something they will discuss with potential customers at AGBT but not disclose more widely.

The first assay on Esper (as detailed below, the sophisticated optical platform has the potential to support multiple chemistries) works by a repetitive probing operation to read the panel of targets -- currently thirty but the goal is get to 1000.  At this time these will just be RNA, but in the future protein as well.  Users design a custom panel and the company promises to return a complete reagent kit for it in two weeks.

The part of Esper to truly geek out over is the optical scheme, which uses Synthetic Aperture Optics.   Instead of using an extremely high magnification oil immersion lens, a relatively low magnification air lens is used.  The magic comes from using lasers to create a defined series of interference patterns on the sample.  These images can then be combined computationally using proprietary algorithms to generate extremely high resolution synthetic images.  CTO and co-founder Josh Ryu walked me through how an 100X oil immersion objective can image about 10 cells per minute because it must capture 20-30 Z-planes for each image.  In contrast, the Synthetic Aperture Optics approach generates the data without any explicit Z-stacking at 1000 cells per minute and a final lateral resolution of 250 nanometers.  Z-stacking is unnecessary since the wider angle lens possesses sufficient depth-of-field to image all of the thickness of a sample.

The system comes with a suite of different software tools and also can export a number of tables in CSV format such as a spot table of location, intensity and quality score as well as a cell by feature matrix scoring all the features by cell.  This feature matrix is intended to be used by emerging tools such as Scanpy and Squidpy as well as being able to be converted to single cell data formats such as Loom and SingleCellExperiment

The initial instrument will have a 300 square millimeter coverslip and options to image all of it or specific regions of interest.  It has been tested on a wide range of fresh and frozen mammalian tissues; FFPE is planned for the near future.

Rebus has already sold early access units in both the U.S. and Europe and plans to commercialize the technology globally.  CEO Paul Sargeant called AGBT "an anchor event for us".

A really fun bit is in the question I failed to ask initially, but Director of Marketing Erin Cline Davis was happy to fill me in on -- and then drove the soundtrack for the rest of this writing exercise.  Why Esper?  

She notes that "Esper" is close to Romance roots for "hope" such as "esperar" in Spanish and its where the universal language effort Esparanto gets its name ("one who hopes") -- brother #1 tried to learn it once and I picked up a few words (now sadly forgotten).  The company believes they are delivering on "the great hope we believe spatial omics has for advancing biology".

But another fun resonance is with Vesper, the evening star -- a reference illumination point in a large field of stars -- much as Rebus is using specific illumination to reveal a large field of cells.

Neither of those would have me cueing up Vangelis -- that would be in the opening credits scene of Blade Runner where Deckard (Harrison Ford) uses "Esper Photo Analysis".   A highly favored soundtrack from a favorite movie -- one that has visual echoes in countless sci-fi movies hence & a key person in realizing that look married my father's sister!

Names aren't the most critical part of a product, but they are important -- and it's nice to see a company having fun with it.

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